Anti-cancer Agents In Medicinal Chemistry[JOURNAL]
Sun
200 papers
Marine-Derived Dual BTK-FGFR Inhibitors: Pioneering a New Era of Precision Oncology Therapeutics.
Kundral S, Kumar A, Gupta P … +2 more , Bodla R, Kumar D
Anticancer Agents Med Chem · 2026 Jun · PMID 42261147 · Publisher ↗
INTRODUCTION: The secondary metabolites produced under the extreme and competitive conditions in the ocean represent a rich and varied source of structurally diverse and biologically active compounds, which have tremendo...
INTRODUCTION: The secondary metabolites produced under the extreme and competitive conditions in the ocean represent a rich and varied source of structurally diverse and biologically active compounds, which have tremendous therapeutic potential. Among others, marine invertebrates continue to yield numerous MNPs with notable anticancer properties. Most of these compounds remain an underexplored reservoir for novel drug discovery. METHODS: This study covers indepth literature study (2015-2025) on Marine-Derived Dual BTK-FGFR Inhibitors. Relevant studies were retrieved from databases including ScienceDirect, PubMed, and Google Scholar. Closely related 110 studies on Marine-Derived Dual BTK-FGFR Inhibitors were included, while unrelated works were excluded. RESULTS: Marine-derived compounds with functional groups, including peptides, terpenoids, alkaloids, and polyketides, have also been shown to inhibit the BTK/FGFR pathway. Several compounds are currently in the preclinical or early-phase of clinical development and show cytotoxicity against multiple cancer cell lines. Computational simulations have predicted bioactivity, refined the model of molecular interactions, and assisted in identifying scaffolds for use in the development of targeted therapies. DISCUSSION: The marine-derived metabolites display unusual chemical scaffold structures that modify BTK and FGFR activity in a very effective manner and decrease the growth of cancer cells. They were selected as potential lead candidates for precision oncology therapies based on computational analyses and newly developing evidence supporting their efficacy as kinase inhibitors. CONCLUSION: Marine invertebrates may provide an exciting source for developing anticancer therapies, as their metabolites are selective modifiers of the BTK and FGFR pathways. Furthermore, when coupled with computational approaches, the integration of marine pharmacology can expedite the identification of strong marinebased therapeutic agents.
Immunohistochemical Evaluation of PD-L1 Expression in Complex Atypical Hyperplasia and Early-Stage Endometrial Cancer.
Akman L, Acar M, Serin G … +5 more , Tureyici L, Yildirim N, Zekioglu O, Karaca B, Terek MC
Anticancer Agents Med Chem · 2026 Jun · PMID 42261146 · Publisher ↗
INTRODUCTION: The study aims to evaluate programmed cell death ligand-1 (PD-L1) expression in complex atypical hyperplasia and early-stage endometrial cancer and to assess its association with tumor grade. MATERIALS AND...
INTRODUCTION: The study aims to evaluate programmed cell death ligand-1 (PD-L1) expression in complex atypical hyperplasia and early-stage endometrial cancer and to assess its association with tumor grade. MATERIALS AND METHODS: This retrospective study was conducted at a single tertiary university hospital and included hysterectomy specimens obtained between 2010 and 2020. A total of 80 cases were analyzed: 20 with complex atypical hyperplasia and 60 with Stage IA endometrioid endometrial cancer, comprising 20 Grade 1, 20 Grade 2, and 20 Grade 3 tumors. All specimens underwent immunohistochemical staining with the PD-L1 (22C3) antibody, and PD-L1 expression was assessed using the combined positive score. RESULTS: PD-L1 expression was absent in complex atypical hyperplasia but present in 4 of 20 Grade 1 cases (20%), 6 of 20 Grade 2 cases (30%), and 16 of 20 Grade 3 cases (80%). PD-L1 positivity increased significantly with higher tumor grade (p < 0.001). No significant associations were identified between PD-L1 expression and patient age, tumor diameter, depth of myometrial invasion, endometrial confinement, or lymphovascular invasion. DISCUSSION: PD-L1 expression appears to be detectable in early-stage endometrioid endometrial cancer and may increase with tumor grade, suggesting early immune checkpoint activity. CONCLUSION: PD-L1 expression may be associated with tumor grade in early-stage endometrioid endometrial cancer. However, its clinical significance remains unclear. These findings may be relevant in the context of fertility- preserving management and require further investigation.
Bioactive Constituents and Potential Cytotoxic Activities of Green Microalgae: Desmodesmus spp. from a Jordanian Isolate.
Al-Halaseh LK, Al-Samydai A, A Sweiss M … +3 more , Al-Qaraleh M, Akram Alsoub D, Carradori S
Anticancer Agents Med Chem · 2026 May · PMID 42227490 · Publisher ↗
INTRODUCTION/OBJECTIVES: Conventional anticancer agents have numerous limitations, and developing innovative agents to treat cancer places a heavy burden on the global health economy. The current study aims to explore su...
INTRODUCTION/OBJECTIVES: Conventional anticancer agents have numerous limitations, and developing innovative agents to treat cancer places a heavy burden on the global health economy. The current study aims to explore sustainable and alternative sources for cancer therapy. OBJECTIVES: This study aims to investigate the phytoconstituents and biologically active compounds in green microalgae and to explore their potential cytotoxicity. METHODS: Algae were isolated from a Jordanian aquatic region, purified, and identified based on the 18S rRNA and Internal Transcribed Spacer (ITS) DNA markers. The lyophilized biomass was extracted by maceration and ultrasonication-assisted shaking, and then the phytoconstituents were identified via HPLC/MS-MS. Cytotoxicity and cell viability assays were performed to evaluate the cytotoxicity of the algal crude extract against normal Human Umbilical Vein Endothelial cell line EA (HUVEC; cat. no. CRL-1730; ATCC), grade IV Prostatic Adenocarcinoma cell line PC3 (CRL-1435), and Human Pancreatic Ductal Adenocarcinoma cell line (PANC1, CRL-1469). RESULTS: The results revealed the presence of several biologically active compounds in the algal aqueous extract, such as fatty acids, amino acids, nucleic acids, terpenoids, coumarins, flavonoids, and polyphenols such as scopoletin, gingerol, and tanacetol. The MTT assays revealed a biocompatibility of the natural remedy with the normal cell line HUVEC, and a dose-related response pattern was observed against cancerous Pancreatic and Prostatic Adenocarcinoma cell lines. The computed IC50 for Pancreatic, Prostatic, and Normal Epithelial cells was 47.7, 56.3, and 217.5 mg/mL, respectively. DISCUSSION: The richness of bioactive compounds that are classified into diverse secondary metabolite families indicates their potential biological and pharmacological activities. The MTT assay results indicate selective cytotoxicity of the extract against Prostatic and Pancreatic cancer cell lines, with the latter showing more sensitivity to the treatment. The high IC50 values of the normal epithelial cell line express its resistance; therefore, the treatment is biocompatible. CONCLUSION: Green microalgae, with their bioactive components, could be a promising approach for a sustainable, innovative therapy for Prostatic and Pancreatic cancers; further, advanced research is highly recommended.
Hsp27 Protects Triple-Negative Breast Cancer Cells against Carboplatin-Induced Cytotoxicity via the Maintenance of Late-Stage Autophagy.
Arslan MA
Anticancer Agents Med Chem · 2026 May · PMID 42227489 · Publisher ↗
INTRODUCTION: Triple-Negative Breast Cancer (TNBC) is a highly aggressive subtype of breast cancer associated with poor prognosis and limited treatment options. Due to the lack of targetable receptors, standard chemother...
INTRODUCTION: Triple-Negative Breast Cancer (TNBC) is a highly aggressive subtype of breast cancer associated with poor prognosis and limited treatment options. Due to the lack of targetable receptors, standard chemotherapy remains the main treatment for TNBC. Heat shock proteins and (macro)autophagy are fundamental stressresponsive systems involved in oncogenesis and increasingly recognized to act in a coordinated manner. This study aimed to investigate the role of Hsp27 in autophagy regulation in response to carboplatin in TNBC cells. METHODS: The IC50 of carboplatin was determined using WST-8 assay. Hsp27 was silenced via siRNA transfection. Autophagic activity was evaluated by Western blot analysis of LC3-II and p62. Cell death was measured using Annexin V-based flow cytometry. RESULTS: Autophagic flux assays conducted with the autophagy inhibitor bafilomycin A1 revealed that Hsp27 depletion blocks the late stage of carboplatin-induced autophagy, as demonstrated by elevated LC3-II levels not further increasing with bafilomycin A1 treatment but remaining unchanged. Additionally, LC3-II accumulation in Hsp27-silenced cells increased in a dose-dependent manner with carboplatin, with 1 mM carboplatin resulting in peak LC3-II levels, accompanied by 50.7% increase in cell death compared to control cells. Collectively, Hsp27 confers cytoprotection against carboplatin-induced toxicity in MDA-MB-231 cells by promoting latestage autophagy. DISCUSSION: Given the aggressive nature of TNBC and its limited treatment options, our findings suggest that targeting Hsp27 has the potential to enhance the efficacy of carboplatin chemotherapy by suppressing cytoprotective autophagy. CONCLUSION: Our findings demonstrate that depletion of Hsp27 sensitizes human TNBC cells to carboplatininduced cell death through inhibition of late-stage autophagy.
Acidic Tumor Microenvironment Promotes 5-Fluorouracil Resistance Via Lactate-Driven HIF-1α/MCT4 Activation and Epigenetic Remodeling in Gastric Cancer.
Niu Z, She T, Wu X … +1 more , Li R
Anticancer Agents Med Chem · 2026 May · PMID 42227488 · Publisher ↗
INTRODUCTION: Tumor acidosis is associated with poor therapeutic response. Yet, it remains unclear whether 5-fluorouracil (5-FU) resistance in gastric cancer is driven by low extracellular pH per se or by lactate as a si...
INTRODUCTION: Tumor acidosis is associated with poor therapeutic response. Yet, it remains unclear whether 5-fluorouracil (5-FU) resistance in gastric cancer is driven by low extracellular pH per se or by lactate as a signaling metabolite. METHODS: The human gastric cancer cell line AGS was exposed to extracellular acidosis (pH 6.6; short-term or chronic) or exogenous lactate at neutral pH. 5-FU sensitivity, apoptosis, and lactate production were assessed. Extracellular pH was buffered with 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES); lactate metabolism/ export was disrupted by LDHA inhibition (FX11) or siRNA-mediated MCT4 knockdown. Global histone methylation was analyzed by Western blot, and qPCR quantified H3K4me3 and H3K27me3 occupancy at SLC16A3 (MCT4) and LDHA promoters. RESULTS: Acidosis reduced 5-FU sensitivity, increased lactate output, suppressed apoptosis, and activated hypoxia- inducible factor 1 alpha (HIF-1α)/monocarboxylate transporter 4 (MCT4) signaling. Buffering pH or inhibiting lactate synthesis/export restored 5-FU sensitivity, indicating a reversible, metabolism-dependent phenotype. Under neutral pH, exogenous lactate alone induced reduced 5-FU sensitivity and activated HIF-1α signaling, supporting a pH-independent role for lactate. Acid exposure increased global H3K27me3 and H3K9me3, which normalized after buffering, whereas SLC16A3 and LDHA promoters showed H3K4me3 enrichment with reduced H3K27me3. DISCUSSION: These findings suggest that acidic stress is transduced through lactate signaling to selectively activate chromatin at lactate-metabolism genes, stabilizing an adaptive survival program under chemotherapy. CONCLUSION: Lactate signaling, rather than low pH alone, underlies a reversible 5-FU-resistant state in gastric cancer cells and may be mitigated by targeting lactate metabolism and/or extracellular pH control.
Pyruvate Kinase M2 in Glioblastoma: A Dual Role in Tumor Metabolism and Nuclear Regulation with Therapeutic and Medicinal Chemistry Insights.
Kumar R, Mishra PS, Patel S
Anticancer Agents Med Chem · 2026 May · PMID 42227487 · Publisher ↗
INTRODUCTION: Glioblastoma (GBM) is a high-grade primary brain tumor with a high proliferation rate, metabolic reprogramming, and unresponsiveness to existing therapeutic interventions. One of the most important glycolyt...
INTRODUCTION: Glioblastoma (GBM) is a high-grade primary brain tumor with a high proliferation rate, metabolic reprogramming, and unresponsiveness to existing therapeutic interventions. One of the most important glycolytic enzymes is pyruvate kinase M2 (PKM2), which plays two roles in GBM: controlling tumor metabolism and nuclear gene expression. The complexity of PKM2 functions is important in the formulation of effective targeted treatments against GBM. METHODS: A comprehensive search of electronic databases such as PubMed, Scopus, Web of Science, and Google Scholar was conducted from inception until 2025. The keywords used were PKM2, glioblastoma, cancer metabolism, and therapeutic targeting. The screening and selection of studies were based on their relevance to the molecular biology of PKM2, its metabolic and nuclear functions, and GBM therapeutic approaches. RESULTS: The outcomes show that PKM2 enhances the Warburg effect in GBM, maintaining glycolytic flux and biosynthetic pathways that support tumor growth under hypoxic conditions. Moreover, PKM2 is associated with proliferation-, stemness-, and immune-evasion-related gene expression. Small-molecule activators and inhibitors, RNA-based therapies, and advanced drug-delivery systems that bypass the blood-brain barrier are therapeutic approaches for targeting PKM2. Medicinal chemistry initiatives have optimized PKM2 modulators, but challenges remain regarding isoform selectivity and effective brain penetration. DISCUSSION: The discussion of PKM2 reveals that it has both metabolic and nuclear functions, making it a promising therapeutic target. However, the difficulties in specific targeting and delivery require combined solutions using molecular, pharmacological, and nanotechnological methods. CONCLUSION: In general, the bifunctional metabolic and nuclear characteristics of PKM2 indicate its relevance as a therapeutic target in glioblastoma, suggesting that combined approaches are needed to support clinical translation.
Design and Development of Chitosan-Based Nanocomposite Films Enriched with Tailored AgNPs Derived from Cassia fistula Flower Extract for Biotherapeutic Applications.
Arland SE, Kumar J
Anticancer Agents Med Chem · 2026 May · PMID 42227486 · Publisher ↗
INTRODUCTION: Chitosan (CS) is a natural biopolymer widely appreciated for its versatile biological attributes, such as biocompatibility and biodegradability, making it an alternative for biomedical applications. The rec...
INTRODUCTION: Chitosan (CS) is a natural biopolymer widely appreciated for its versatile biological attributes, such as biocompatibility and biodegradability, making it an alternative for biomedical applications. The recent trend in nanotechnology has led to the development of CS based composite biomaterials by incorporating the phytochemicals and biosynthesized silver nanoparticles (AgnPs). These modifications to the CS backbone broaden its biomedical applications. METHODS: The CS embedded nanocomposite film (CS_CFF_AgNPs) was developed via the incorporation of silver nanoparticles (AgNPs) derived from Cassia fistula flower extracts. The developed nanofilm was characterized using multiple analytical techniques. Different parameters of physicochemical properties were studied. The films underwent in vitro biological assays of antioxidant potential via DPPH, and antimicrobial efficacy via agar well diffusion method. Additionally, cytotoxicity and scratch assays were performed to determine its woundhealing capabilities. RESULTS: The CS_CFF_AgNPs nanocomposite film exhibited distinct, well-defined physicochemical properties and biotherapeutic activity. FTIR, XRD, and TGA techniques confirmed its successful fabrication, and enhanced antioxidant activity and notable antibacterial efficacy were observed. Cytotoxicity and scratch assays revealed high cell viability and accelerated cell migration, supporting its regenerative potential. DISCUSSION: The improved therapeutic activity of the developed CS_CFF_AgNPs nanocomposite is likely due to the synergistic effects of CS, CFF phytochemicals and biogenic AgNPs, as evidenced by improved DPPH and ZOI along with accelerated wound healing. CONCLUSION: Overall, this study displays the promising potential of the CS_CFF_AgNPs nanocomposite as a sustainable and effective functional biomaterial. The observed enhanced antioxidant, antimicrobial, and woundhealing properties supports its viable candidature for advanced biomedical applications, especially in regenerative medicine and infection management.
Egyptian Cobra Venom and Honey Bee Venom Treatment Ameliorated Levels of Neuropilin 1, Angiopoietin 2, and DNA Topoisomerase II Binding Protein 1 in Induced Hepatocellular Carcinoma in Albino Rats.
M Abas AS, Abdallah Awad D, A H Abd Elhameed H
Anticancer Agents Med Chem · 2026 May · PMID 42227485 · Publisher ↗
INTRODUCTION: Hepatocellular carcinoma (HCC) is a critical health problem that is classified as the fifth most prevalent malignancy in the world. Our study aimed to investigate the anti-tumor activity of the Egyptian cob...
INTRODUCTION: Hepatocellular carcinoma (HCC) is a critical health problem that is classified as the fifth most prevalent malignancy in the world. Our study aimed to investigate the anti-tumor activity of the Egyptian cobra venom and honey bee venom in the treatment of DENA-induced HCC in rats compared to the chemotherapeutic drug cisplatin. METHODS: 70 male adult albino rats were randomly placed into seven groups. Group 1 served as a negative control. Group 2 received 0.1 LD50 snake venom (SV). Group 3 received 0.1 LD50 bee venom (BV). While the other four groups received diethylnitrosamine (DENA) to induce HCC, they were subsequently divided as follows: Group 4 served as a positive control group (HCC), and the other three remaining groups represented the treated groups. Group 5: snake venom-treated group (HCC+SV). Group 6: bee venom-treated group (HCC+BV). Group 7: Cisplatin-treated group (HCC+CIS). RESULTS: DENA induced HCC, as proved by a significantly high increase in AST, ALT, GGT, and ALP activities and a decrease in total protein and albumin contents. Also, significantly elevated levels of urea, creatinine, proinflammatory cytokine (IL-1β), and tumor markers (NRP1, ANG2, TOPBP1) in comparison to the negative control group. Treatment of HCC rats using snake venom, bee venom, and cisplatin revealed a significant decrease in liver enzymes and tumor markers. The venoms showed a potent synergistic anti-tumor effect by significantly upregulating the expression of pro-apoptotic gene Caspase 3 and downregulating the expression of the anti-apoptotic gene (Bcl-2) in comparison to the positive control HCC group. Our findings were confirmed by histological analysis and immunohistochemical Caspase-3 expression. DISCUSSION: Both snake venom and bee venom have anti-inflammatory, apoptotic, and anticancer effects against induced HCC. However, the use of BV is more effective and safer than SV. CONCLUSION: Egyptian cobra venom and honey bee venom may serve as an apoptotic stimulator, and can be considered as novel potential therapeutic against HCC.
Synergistic Anticancer and Antibacterial Activities of Marine Sponge Extracts Combined with Fungal-Synthesized Silver Nanoparticles from Aspergillus flavus.
Alqaraleh M, Al-Samydai A, Carradori S … +5 more , Khleifat KM, Al-Najjar BO, Alqaraleh S, Alhmoud JF, Al-Rawashde FA
Anticancer Agents Med Chem · 2026 May · PMID 42220140 · Publisher ↗
INTRODUCTION: This study explores the cytotoxic efficacy of combining Dysidea tuapokere or Agelas conifera extract with silver nanoparticles (AgNPs) synthesized from Aspergillus flavus on various cancer cell lines and pa...
INTRODUCTION: This study explores the cytotoxic efficacy of combining Dysidea tuapokere or Agelas conifera extract with silver nanoparticles (AgNPs) synthesized from Aspergillus flavus on various cancer cell lines and pathogenic bacteria. METHODS: AgNPs were characterized using zeta potential, dynamic light scattering, and scanning electron microscopy. The chemical composition of the marine sponge extracts was analyzed using LC-MS/MS. Cancer cell lines (PANC-1, A549, MCF-7, and HT-29) and normal HUVEC cells were tested for cytotoxicity using MTT assays to calculate selectivity indices (SI). Antibacterial activity was assessed against antibiotic-resistant strains. Docking studies were conducted to investigate the binding of sponge-derived compounds to EGFR and TrkA receptors. RESULTS: Characterization of AgNPs revealed a mean particle size of 69.455 nm, a zeta potential of -28 mV, and a polydispersity index (PDI) of 0.177. After lyophilization, the particle size increased to 144.555 nm and the PDI to 0.335. SEM showed silver particles below 0.5 μm. Combining Dysidea tuapokere or Agelas conifera extracts with AgNPs enhanced antiproliferative activity. This activity was relatively selective for cancer cells over HUVEC cells, particularly for PANC-1 (SI: 254.74) and A549 (SI: 204.85). LC-MS/MS identified bioactive components. Docking showed favorable binding to EGFR and TrkA. Dysidea tuapokere extract with AgNPs significantly enhanced the inhibition of S. xylosus, K. oxytoca, and P. aeruginosa. DISCUSSION: The synergistic antiproliferative effect selectively targets cancer cells. The combined treatment may have broad-spectrum bioactivity. CONCLUSION: This study highlights the synergistic potential of marine sponge extracts combined with AgNPs.
Photoactivated Aluminium Phthalocyanine Drives Oxidative Stress and Apoptosis in Human Oesophageal Cancer Stem Cells.
Didamson OC, Abrahamse H
Anticancer Agents Med Chem · 2026 May · PMID 42163599 · Publisher ↗
INTRODUCTION: Photodynamic therapy (PDT), a light-based treatment strategy, has demonstrated efficiency against several cancers. However, the therapeutic effect of aluminium phthalocyanine chloride tetrasulfonate (AlPcS4...
INTRODUCTION: Photodynamic therapy (PDT), a light-based treatment strategy, has demonstrated efficiency against several cancers. However, the therapeutic effect of aluminium phthalocyanine chloride tetrasulfonate (AlPcS4Cl)-mediated PDT, which induces oxidative stress and potentiates apoptotic activity in oesophageal Cancer Stem Cells (CSCs), is limited. Therefore, this study examined the effects of AlPcS4Cl in promoting oxidative stress and apoptotic cell death in oesophageal CSCs. METHODS: The CSCs were isolated from HKESC-1 cells and were categorised into control and treatment groups. The CSCs treatment groups were exposed to AlPcS4Cl. Twenty-four hours after PDT, the effects of AlPcS4Cl on oesophageal CSCs in inhibiting cell growth, promoting oxidative stress, and cell death were evaluated. Cell viability was assessed using a viability assay. A cellular Reactive Oxygen Species (ROS) assay was used to determine the induction of oxidative stress. Rhodamine-123 flow cytometry analysis was performed to evaluate mitochondrial membrane potential. The Annexin V-FITC/PI assay was used to investigate the cell death mechanism, and a Caspase-Glo 3/7 luminescence assay was employed to assess caspase activities. RESULTS: The results showed altered cell morphology, increased cytotoxicity, decreased cell viability, high ROS generation, impaired mitochondrial membrane, induced apoptosis, and increased caspase 3/7 activity in oesophageal CSCs treated with AlPcS4Cl-PDT compared to the control cells. DISCUSSION: The finding implies that AlPcS4Cl-PDT promotes oxidative stress and apoptosis in oesophageal CSCs, supporting its application for the elimination of CSCs and as an effective anticancer agent. CONCLUSION: This study demonstrates the promising use of AlPcS4Cl-PDT in eradicating oesophageal CSCs and improving prognosis.
A Study of iNOS and PCNA Expression on the Aggressiveness of Oral Squamous Cell Carcinoma (OSCC).
Ali AN, Sayed MH, Shaker WM … +2 more , Rokaya D, Arafa MM
Anticancer Agents Med Chem · 2026 May · PMID 42163598 · Publisher ↗
INTRODUCTION/OBJECTIVE: Oral Squamous Cell Carcinoma (OSCC) is one of the world's most aggressive cancers. Large-scale NO generation is facilitated by Inducible Nitric Oxide Synthase (iNOS) in chronic inflammatory diseas...
INTRODUCTION/OBJECTIVE: Oral Squamous Cell Carcinoma (OSCC) is one of the world's most aggressive cancers. Large-scale NO generation is facilitated by Inducible Nitric Oxide Synthase (iNOS) in chronic inflammatory diseases, including cancer. The 36-kDa non-histone nuclear peptide, also known as Proliferating Cell Nuclear Antigen (PCNA), is important for DNA replication. In human OSCC, iNOS and PCNA are useful indicators of induction, progression, and cell proliferation that influence the aggressiveness and growth rate of cancer. Thus, this study aimed to compare the expression of PCNA and iNOS in various OSCCs. METHODS: The study design was a retrospective study using 30 tissue blocks from OSCC patients immunohistochemically stained with iNOS and PCNA antibodies and divided into ten well-differentiated, ten moderatelydifferentiated, and ten poorly-differentiated OSCC. PCNA-positive cells and iNOS infiltration intensity were measured. One-way ANOVA with multiple comparisons was done using Tukey's Post Hoc Test to compare the expression of PCNA and iNOS in various OSCCs, and a Chi-square test was performed for score values in various OSCCs. A P-value < 0.05 was considered significant. RESULTS: With varying histopathological grades of OSCC, the infiltration intensity of iNOS increased from weak expression in well-differentiated OSCC (2.3 ± 0.78) to strong expression in poorly-differentiated OSCC (5 ± 1.18). In addition, PCNA-positive cells were observed and showed higher expression, increasing from weak expression in well-differentiated OSCC (466 ± 31.35) to strong expression in poorly-differentiated OSCC (673 ± 76.27). It was revealed that the expression increased as OSCC progressed (P-value < 0.01). DISCUSSION: The identification of reliable biomarkers that can predict tumor behavior, prognosis, and response to therapy is critical for improving patient outcomes. In this context, they are considered key immunohistopathological markers in OSCC. Understanding the role of iNOS and PCNA in OSCC can enhance diagnostic accuracy and offer new avenues for targeted therapies. These markers may serve not only as tools for evaluating tumor proliferation and invasiveness but also as indicators for therapeutic response, particularly in the context of novel anti-cancer therapies aimed at modulating the tumor microenvironment or cell cycle regulation. Furthermore, their utility in identifying high-risk patients with a propensity to metastasize underscores their clinical relevance in stratifying patient care and informing personalized treatment plans. CONCLUSIONS: These results demonstrated that elevated iNOS and PCNA expression may serve as prognostic indicators for OSCC. This will improve clinical decision-making, guiding therapeutic interventions and enhancing patient prognosis in OSCC management.
Network Pharmacology, Molecular Docking, and Wnt Signaling-Associated Gene Expression Modulation Effects of New Anti-Colorectal Cancer Agents.
Alagumuthu M, Rajavel R, Patel S
Anticancer Agents Med Chem · 2026 May · PMID 42152280 · Publisher ↗
INTRODUCTION: Colorectal Cancer (CRC) remains a major global health challenge due to the emergence of resistance to current therapies. Identifying selective compounds that effectively trigger apoptosis in cancer cells wh...
INTRODUCTION: Colorectal Cancer (CRC) remains a major global health challenge due to the emergence of resistance to current therapies. Identifying selective compounds that effectively trigger apoptosis in cancer cells while sparing normal tissues is therefore essential. METHODS: Candidate molecules were identified through virtual screening and network-based prioritization targeting p53, BAX, and BCL-2. Molecular docking and Molecular Dynamics (MD) simulations were used to validate binding stability and target specificity. In vitro assays were conducted on human CRC (HCT116) and normal colon fibroblast (CCD-18Co) cells to evaluate cytotoxicity, proliferation, and DNA fragmentation. QRTPCR performed gene expression analyses of p53, BAX, and BCL-2 following treatment with 25-100 μg/mL of each compound for 12-72 h. RESULTS: Among the screened compounds, LC_60 emerged as the most potent and selective candidate, exhibiting a remarkably low IC₂⁽ (0.0128 μg/mL) toward HCT116 cells and negligible toxicity toward CCD-18Co cells (CC₂⁽ = 125 μg/mL), yielding an exceptionally high selectivity index (SI ≈ 9,766). Docking and MD simulations confirmed strong and stable interactions of LC_60 with BAX and β-catenin, supporting its dual role in apoptosis induction and Wnt pathway inhibition. LC_60 treatment significantly upregulated p53 and BAX while downregulating BCL-2, consistent with activation of intrinsic apoptotic signaling. DISCUSSION: LC_60's pronounced potency and outstanding selectivity underscore its ability to selectively modulate apoptosis in malignant colon cells while sparing normal fibroblasts, suggesting a strong therapeutic window and tumor specificity. CONCLUSION: Collectively, the findings identify LC_60 as a highly selective, multitargeted lead compound that activates p53-BAX-mediated apoptosis and inhibits oncogenic Wnt signaling, establishing it as a promising scaffold for further preclinical development in colorectal cancer management.
Computational Design, Synthesis, and In Vitro Evaluation of Novel Piperazine-Based HDAC Inhibitors as Potential Breast Cancer Therapeutics.
Dizdarevic S, Ruzic D, Srdic-Radic T … +1 more , Vujić Z
Anticancer Agents Med Chem · 2026 May · PMID 42152279 · Publisher ↗
INTRODUCTION: Limited treatment options and poor prognosis create a need for new therapies for triplenegative breast cancer. Modulating lysine acetylation of histone and non-histone proteins via histone deacetylase inhib...
INTRODUCTION: Limited treatment options and poor prognosis create a need for new therapies for triplenegative breast cancer. Modulating lysine acetylation of histone and non-histone proteins via histone deacetylase inhibitors is a promising strategy in cancer therapy. This study aimed to design, synthesize, and test novel panHDAC inhibitors in vitro, building on our previous research. METHODS: Compound design was based on a previously validated diphenylmethyl piperazine scaffold, used as a template for further modifications. In silico studies included molecular docking and pharmacokinetic profiling for absorption, distribution, metabolism, excretion, and toxicity. Compounds identified from these analyses were synthesized, tested for in vitro enzymatic inhibition, and evaluated for cytotoxicity on cancer cell lines using the MTT assay. RESULTS: Compound 8o had the strongest HDAC inhibitory profile. It was highly potent against HDAC6 (IC50 = 18.5 nM) and active against HDAC1 and HDAC8 (IC50 = 430 nM and 1620 nM, respectively). Compound 8p also inhibited HDAC6 (IC50 = 54 nM) but was less potent against the nuclear isoforms. Both compounds were less active than trichostatin A. In the cytotoxicity assay, 8o and 8p reduced the viability of triple-negative breast cancer cells in a dosedependent manner. Compound 8o was the most active (IC50 = 6.74 μM on MDA-MB-231), exceeding the effect of tubastatin A. Moderate activity was seen on MDA-MB-468 cells. DISCUSSION: In vitro enzymatic assays showed that compound 8o strongly inhibited HDAC6, similar to the reference compound 8b. However, its cellular activity did not exceed 8b, suggesting that factors other than target engagement may limit its cell efficacy. These findings show the need to combine biochemical and physicochemical data when optimising HDAC inhibitors for triple-negative breast cancer. CONCLUSION: Compounds 8o and 8p were identified as potent panHDAC inhibitors. They demonstrated cytotoxicity against triple-negative breast cancer cells. This provides a promising foundation for future structural optimization and preclinical development.
Emerging Frontiers in Prostate Cancer Diagnostics: Nanolaser-Guided Nanotechnology and Computational Biology for Biomarker Surveillance.
Chauhan SB, Singh I, Kalra Y … +1 more , Jain C
Anticancer Agents Med Chem · 2026 May · PMID 42152278 · Publisher ↗
INTRODUCTION: Prostate cancer remains a leading cause of cancer-related mortality in men, with early and accurate diagnosis being crucial for effective management. This review explores the convergence of nanolaser- assis...
INTRODUCTION: Prostate cancer remains a leading cause of cancer-related mortality in men, with early and accurate diagnosis being crucial for effective management. This review explores the convergence of nanolaser- assisted nanotechnology and computational biology as innovative strategies for biomarker surveillance in prostate cancer. METHODS: A systematic review of recent peer-reviewed literature from PubMed, Scopus, and Web of Science was conducted, focusing on studies published between 2015 and 2024. Keywords included "prostate cancer," "nanolaser diagnostics," "nanotechnology," "computational biology," and "biomarker detection." Selected articles were analyzed for advancements in diagnostic platforms, biomarker sensitivity, and integration with computational models. RESULTS: Findings indicate that nanolaser-guided nanotechnologies offer ultra-sensitive detection of prostatespecific antigen and emerging molecular biomarkers with improved specificity compared to conventional assays. Computational biology approaches, including machine learning and systems biology models, enhance data interpretation, enable multi-biomarker integration, and support predictive analytics. Hybrid systems demonstrate potential for real-time monitoring, non-invasive sampling, and precision diagnostics. DISCUSSION: The integration of nanolaser technologies with computational biology addresses key limitations of current diagnostic practices, including false positives, delayed detection, and limited biomarker scope. However, challenges such as scalability, regulatory approval, and standardization remain significant barriers. Collaborative research that bridges engineering, computational sciences, and clinical oncology is essential to translate these technologies into practice. CONCLUSION: Nanolaser-guided nanotechnology, coupled with computational biology, represents a promising frontier in prostate cancer diagnostics. Together, these tools hold the potential to advance biomarker surveillance, improve diagnostic accuracy, and pave the way for personalized oncology.
Role of Cellular Senescence in Melanoma: Implications for Tumor Progression and Therapy.
Pan H, Jiang J, Zhang J … +5 more , Jia Z, Wang Q, Zhang J, Luo Y, Yu B
Anticancer Agents Med Chem · 2026 May · PMID 42152277 · Publisher ↗
INTRODUCTION: Aging is the most significant risk factor for cancer, with melanoma incidence and mortality rising with advancing age. Cellular senescence, a hallmark of aging, plays dual roles in melanoma progression, exe...
INTRODUCTION: Aging is the most significant risk factor for cancer, with melanoma incidence and mortality rising with advancing age. Cellular senescence, a hallmark of aging, plays dual roles in melanoma progression, exerting both tumor-suppressive and tumor-promoting effects via the senescence-associated secretory phenotype (SASP) and its complex influence on the tumor microenvironment (TME). METHODS: Relevant literature was retrieved from PubMed, Web of Science, and Scopus from 2002 up to June 2025, using keywords related to melanoma, cellular senescence, SASP, senolytics, and immunotherapy. Studies were evaluated for mechanistic insights, preclinical evidence, and translational relevance. RESULTS: Evidence indicates that senescent cells in melanoma can suppress tumor growth through cell cycle arrest and immune activation, yet also promote immune evasion, metastasis, and therapy resistance through SASP-mediated pathways. Traditional and targeted therapies can induce senescence, while senolytic agents, particularly in combination with immune checkpoint inhibitors, show promise in eliminating therapy-induced senescent cells and enhancing anti-tumor immunity in preclinical models. DISCUSSION: The therapeutic potential of senescence modulation in melanoma is tempered by key challenges, including the pronounced heterogeneity of senescent cells, SASP's context-dependent effects, and limited melanoma- specific clinical trial data. Strategies to overcome these hurdles include biomarker-driven patient selection, senomorphic modulation, and rational senolytic-immunotherapy combinations. CONCLUSION: Senescence-targeting strategies hold considerable promise for melanoma treatment but require deeper mechanistic characterization and robust early-phase clinical evaluation before routine clinical application. Integrating senescence modulation into precision oncology frameworks may ultimately improve outcomes in melanoma patients.
Development and Characterization of PEGylated β-Carotene-Loaded Liposomes as Radiosensitizers in HepG2 Hepatocellular Carcinoma Cells: In Vitro and In Silico Studies.
Abdel-Moamen H, Abbase ER, El-Khadragy MF … +4 more , Elabed S, Elshopakey GE, Abdel Moneim AE, Shafaa MW
Anticancer Agents Med Chem · 2026 May · PMID 42152276 · Publisher ↗
INTRODUCTION: Hepatocellular Carcinoma (HCC) is a leading cause of cancer death with limited responsiveness to radiotherapy. β-Carotene has chemopreventive properties, but its clinical use is hindered by poor aqueous sol...
INTRODUCTION: Hepatocellular Carcinoma (HCC) is a leading cause of cancer death with limited responsiveness to radiotherapy. β-Carotene has chemopreventive properties, but its clinical use is hindered by poor aqueous solubility and instability. This study developed PEGylated β-carotene-loaded liposomes (PEGLipo- β-Car) as a novel nanocarrier-based radiosensitizer and used in silico modeling to explore its molecular interactions. METHODS: PEG-Lipo-β-Car was prepared via thin-film hydration and characterized (TEM, DLS, FTIR, DSC). Cytotoxicity and radiosensitization were evaluated in HepG2 cells under γ-irradiation (0, 5, 10 Gy) using MTT assays, with synergy quantified via Combination Indices (CI). Molecular docking assessed β-carotene binding to PARP and ATM. RESULTS: PEG-Lipo-β-Car exhibited good colloidal stability (size: 143.4 ± 8.2 nm, PDI: 0.201, EE >94%). At 10 Gy irradiation, it reduced the IC50 from 29.78 to 0.57 μg/mL, a 52-fold enhancement with strong synergy (CI=0.019). Empty liposomes alone conferred significant radiosensitization (~30-fold). Docking revealed β- carotene binds the catalytic sites of PARP (-9.19 ± 0.37 kcal/mol) and ATM (-10.12 ± 0.36 kcal/mol). DISCUSSION: The observed radiobiological synergy may stem from a combined effect of carrier-mediated membrane perturbation and/or ROS amplification, coupled with the potential inhibition of DNA repair pathways by the delivered β-carotene. CONCLUSIONS: PEGylation enhances β-carotene's stability and radiosensitizing efficacy in HCC cells through a combined mechanism involving carrier effects and potential interference with PARP- and ATM-mediated DNA repair. PEG-Lipo-β-Car is a promising candidate for future preclinical evaluation in hepatocellular carcinoma radiotherapy.
Advancing in Acute Promyelocytic Leukemia Therapy Research: The Role of 3-Alkylpyridine Alkaloid Analogs in Overcoming Genetic and Molecular Barriers.
Freitas TR, de Almeida TD, Evangelista FCG … +6 more , de M G Loures C, de S Barbosa C, Maltarollo VG, Viana GHR, de P Varotti F, de P Sabino A
Anticancer Agents Med Chem · 2026 May · PMID 42152275 · Publisher ↗
INTRODUCTION: Acute leukemias are malignant clonal disorders of blood cells, originating in the bone marrow. Acute Promyelocytic Leukemia (APL), when left untreated, progresses unfavorably, often resulting in severe hemo...
INTRODUCTION: Acute leukemias are malignant clonal disorders of blood cells, originating in the bone marrow. Acute Promyelocytic Leukemia (APL), when left untreated, progresses unfavorably, often resulting in severe hemorrhaging. Chemotherapy remains a key therapeutic strategy; however, the need for discovering new antitumor agents is critical. This study aims to evaluate the cytotoxic effects of 16 synthetic analogs of 3-alkylpyridine alkaloids (3-APA) on various APL cell lines and Peripheral Blood Mononuclear Cells (PBMCs), with the goal of identifying promising new therapeutic candidates for APL treatment. MATERIALS AND METHODS: The cytotoxic effects of 16 synthetic 3-APA analogs were assessed on APL cell lines (NB4, NB4-LR2, and HL-60) and PBMC. The MTT assay was used to evaluate the cytotoxic profiles of the compounds. Apoptosis induction and cell cycle arrest were analyzed using flow cytometry. Gene expression changes related to apoptosis (TP53, p21, BAK, Bcl-2, AKT) and oxidative stress (NOX-1, NOX-2, NOX-4, P47-phox) were measured through RT-qPCR. Additionally, chemical similarity analysis via ChEMBL was performed to predict potential molecular targets, including ROS1 and PARP1. RESULTS: The results demonstrated distinct cytotoxic responses among the tested cell lines. All 16 compounds induced apoptosis in the APL cell lines, leading to a notable decrease in the expression of antiapoptotic genes, including p21, Bcl-2, and AKT, which contributed to cell death. Gene expression analysis revealed an increase in oxidative stress markers, particularly NOX-2 and p47-phox in the NB4 cell line, and NOX-1 and NOX-4 in the NB4-LR2 lineage, suggesting potential mechanisms of cellular damage and resistance. DISCUSSION: The 3-APA analogs showed significant cytotoxic effects against APL cell lines, with distinct selectivity profiles. The induction of apoptosis and the downregulation of anti-apoptotic genes underscore the potential of these compounds as promising therapeutic agents. The observed changes in oxidative stress gene expression further suggest a mechanism of action involving oxidative damage, which could contribute to the efficacy of the compounds, especially in overcoming resistance in the ATRA-resistant NB4-LR2 cell line. Additionally, the prediction of ROS1 and PARP1 as potential molecular targets opens new avenues for further investigation. CONCLUSION: This study highlights the potential of 3-APA analogs as effective cytotoxic agents in the treatment of APL. The compounds demonstrated significant apoptotic activity and altered gene expression, particularly in apoptosis regulation and oxidative stress pathways. These findings suggest that 3-APA analogs may serve as valuable candidates for future therapeutic development in APL treatment, warranting further research into their molecular mechanisms and clinical applicability.
Morusin Attenuates Cancer Stemness and Modulates CSC-driven Macrophage Polarization in Cervical Cancer.
Tripathi T, Joshi U, Chaudhary A … +6 more , Janjua D, Kumar S, Tanwar N, Mittal A, Senrung A, Bharti AC
Anticancer Agents Med Chem · 2026 May · PMID 42136212 · Publisher ↗
INTRODUCTION: Cancer stem cells (CSC) role in treatment resistance is well established. CSCs promote M2 macrophage polarization within the tumor microenvironment, creating a pro-tumorigenic feedback loop that sustains CS...
INTRODUCTION: Cancer stem cells (CSC) role in treatment resistance is well established. CSCs promote M2 macrophage polarization within the tumor microenvironment, creating a pro-tumorigenic feedback loop that sustains CSC homeostasis. Therefore, disrupting this cross-talk can be an effective therapeutic strategy. In the present study, we identified Morusin as a potent inhibitor that could impact both cancer stemness and CSCinduced macrophage polarization. METHODS: In silico screening was performed to assess the druggability of Morusin and its binding to stemness markers. Molecular Docking and simulation were performed to check the stability of Morusin binding with markers. To evaluate its effect on cancer stemness, low-adhesion spheroids were treated with Morusin at IC50, followed by qPCR and western blot for stemness markers. To investigate Morusin's influence on CSC-mediated macrophage polarization, innovative transwell co-culture systems were employed to assess the impact of tumor spheroids on macrophage phenotype. RESULT: Molecular docking identified Morusin as a binder of the stemness factors Oct4, Sox2, and Nanog, with MD simulations confirming stable interactions and the strongest binding to Oct4. In an in vitro system, Morusin reduced spheroid size, disrupted spheroidal integrity and self-renewal, and lowered Oct4 and Sox2 levels, proving to be an effective anti-CSC agent. In a transwell system, activated THP1 cells co-cultured with 3D tumorspheres showed enhanced M2 polarization compared to monolayers, whereas Morusin-treated tumorspheres shifted THP1 cells toward an M1 phenotype. DISCUSSION: These findings indicate that Morusin targets both Cervical-CSC stemness and prevents CSCinduced M2 polarization, thus dampening CSC-Macrophage crosstalk. CONCLUSION: These findings indicate that Morusin targets both Cervical-CSC stemness and prevents CSCinduced M2 polarization, thus dampening CSC-Macrophage crosstalk.
Preparation and Characterization of Raloxifene- and Rutin-Co-loaded Chitosan Nanoparticles for the Treatment of Colon Cancer.
Al-Sahlawi F, Al-Samydai A, Alabdali AYM … +3 more , Carradori S, Maki MAMA, Chinnappan S
Anticancer Agents Med Chem · 2026 May · PMID 42136211 · Publisher ↗
INTRODUCTION: Colorectal cancer is a significant health concern with high incidence and mortality rates. Raloxifene (RLX) is a selective estrogen receptor modulator that blocks estrogen receptors, reducing the risk of es...
INTRODUCTION: Colorectal cancer is a significant health concern with high incidence and mortality rates. Raloxifene (RLX) is a selective estrogen receptor modulator that blocks estrogen receptors, reducing the risk of estrogen-dependent cancer growth. Rutin (RT), a naturally occurring flavonoid found in medicinal plants, has attracted attention for its potential role in cancer prevention and treatment, including colon cancer. METHODS: In this study, the nanoparticles were prepared by the ionic gelation method. The synthesized nanoparticles were characterized by release assays and FTIR, SEM, and TEM, while their cytotoxic effects were assessed on the HT-29 colon cancer cell line. RESULTS: The drug loading percentage of RLX/RT/CsNPs was found to be 84% at a 1:2 w/w ratio. SEM and TEM analyses revealed that the RLX/RT/CsNPs exhibited an average size of 57.23 nm with a spherical morphology. Thermogravimetric analysis of the nanoparticles revealed a two-stage weight loss pattern, and the drug release study showed RLX/CsNPs = 44.12%, RLX = 10.68%, and RLX/RT/CsNPs = 47.12% drug release at 24 hrs. DISCUSSION: The IC50 value of RLX/RT/CsNPs was 23.51 ± 0.60 μM, which was significantly lower compared with the IC50 of RLX/CsNPs (IC50 = 252.20 ± 7.80 μM, p < 0.001) and RT/CsNPs (IC50 = 300.51 ± 52.05 μM, p < 0.001) against the HT-29 colon cancer cell lines. CONCLUSION: In conclusion, we developed a new nanoparticle system combining RLX and RT showing favorable physicochemical characteristics and synergistic effects in colon cancer cell lines. The designed NPs can be used as a promising drug therapy against colon cancer.
MicroRNA-21 in Cancer and Fibrosis: Molecular Mechanisms and Therapeutic Progress.
Sharma A, Kaur A, Khan J … +1 more , Pandey H
Anticancer Agents Med Chem · 2026 May · PMID 42099174 · Publisher ↗
MicroRNA-21 (miR-21) is a key regulator of gene expression involved in cancer progression and fibrosis. Its dysregulation promotes cell proliferation, resistance to apoptosis, Epithelial-Mesenchymal Transition (EMT), and...
MicroRNA-21 (miR-21) is a key regulator of gene expression involved in cancer progression and fibrosis. Its dysregulation promotes cell proliferation, resistance to apoptosis, Epithelial-Mesenchymal Transition (EMT), and Extracellular Matrix (ECM) remodeling, making it one of the most widely studied oncomiRs and fibromiRs. Evidence shows that miR-21 contributes to tumor growth, metastasis, and fibrosis by suppressing tumor suppressors such as PTEN and PDCD4 and activating pro-fibrotic pathways, including TGF-β signaling. Its consistent dysregulation highlights its potential as a biomarker for diagnosis, prognosis, and treatment monitoring. Several therapeutic strategies, such as antagomiRs, locked nucleic acids (LNAs), CRISPR-based inhibition, and nanoparticle- or viral-mediated delivery systems, have shown promising preclinical results. Despite advances, challenges remain in translating miR-21 inhibition to clinical use. Key limitations include off-target effects, delivery inefficiencies, and context-dependent variability in miR-21 function. These issues hinder the development of safe and effective miR-21-targeted therapies. MiR-21 plays a central role in cancer and fibrosis and offers significant potential as both a biomarker and therapeutic target. Future research should focus on precision-based approaches, next-generation gene-editing technologies, and improved preclinical models to optimize miR-21 inhibition for clinical application. This review compiles and evaluates current literature on miR-21 biogenesis, regulation, functional roles, and therapeutic targeting across various cancers and organ-specific fibrotic disorders.
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